X chromosome

About: X chromosome is a research topic. Over the lifetime, 9862 publications have been published within this topic receiving 407354 citations. The topic is also known as: GO:0000805 & chrX.

Selection in blood cells from female carriers of the fragile X syndrome: inverse correlation between age and proportion of active X chromosomes carrying the full mutation.

Abstract: We have studied the patterns of mutation and X inactivation in female carriers of a fragile X mutation, to try to correlate them with various phenotypic features. We used a simple assay, which shows simultaneously the size of the mutation, its methylation status, and DNA fragments that represent the normal active and inactive X chromosomes. We have observed an age dependent process, whereby the 'full' fragile X mutation is found preferentially on the inactive X in leucocytes in adult females, but not in younger ones. This phenomenon was not observed in female carriers of a 'premutation', who have little phenotypic expression. Preliminary data suggest that young females who show preferential presence of a full mutation on the active X in leucocytes may be at increased risk for mental retardation. We have also obtained preliminary evidence for an age dependent decrease in the somatic heterogeneity of full mutations, possibly owing to selection for smaller mutated fragments. If confirmed, the latter phenomenon might account for the known decrease with age of the expression of the fragile site. Our observations suggest that a gene whose expression is affected by the presence of a full mutation (possibly the FMR-1 gene) has a cell autonomous function in leucocytes, leading to a slowly progressive selection for cells where the mutation is on the inactive X chromosome.

Variable transfer of Y-specific sequences in XX males

Abstract: A series of twelve XX males and their relatives have been examined by Southern blot analysis with fourteen different Y recombinants. The pattern of Y sequences present shows considerable variation between XX males. Furthermore, on the basis of the terminal transfer model, anomalous patterns of Y sequences are evident in certain XX males in that sequences located as proximal Yp by means of a Y deletion panel are found to be present in the absence of distal sequences. These anomalies can be resolved by proposing that the order of Yp sequences varies in the population in the form of inversion polymorphisms in the Y chromosomes of normal males. Alternatively, it is necessary to invoke multiple recombination events between the X and Y chromosomes to explain the patterns of Y sequences in these XX males. Southern analysis on DNA prepared from flow sorted X chromosomes of XX males indicates that the Y sequences in these patients are linked to X chromosomes.

Meiotic behaviour of the sex chromosomes in three patients with sex chromosome anomalies (47,XXY, mosaic 46,XY/47,XXY and 47,XYY) assessed by fluorescence in-situ hybridization

Abstract: Meiotic studies using multicolour fluorescent in-situ hybridization (FISH) and chromosome painting were carried out in three patients with sex chromosome anomalies (47,XXY; 46,XY/47,XXY and 47,XYY). In the two patients with Klinefelter syndrome, although variable percentages of XXY cells (88.5 and 28.3%) could be found in the pre-meiotic stages, none of the abnormal cells entered meiosis, and all pachytenes were XY. However, the abnormal testicular environment of these patients probably resulted in meiotic I non-disjunction, and a certain proportion of post-reductional cells were XY (18.3 and 1.7%). The fact that none of the spermatozoa were XY also suggests the existence of an arrest at the secondary spermatocyte or the spermatid level. In the XYY patient, most (95.9%) premeiotic cells were XYY. The percentage of XYY pachytenes was 57.9%. The sex chromosomes were either in close proximity (XYY) or the X chromosome was separated from the two Ys (X + YY). A high proportion (42.1%) of post-reductional germ cells were XY. However, only 0.11% of spermatozoa were disomic for the sex chromosomes. In this case, the data suggest the existence of an arrest of the abnormal cells at the primary and the secondary spermatocyte or the spermatid level, giving rise to the continuous elimination of abnormal cells in the germ-cell line along spermatogenesis. The fact that the proportion of diploid spermatozoa was only increased in one of the three cases (XXY) is also suggestive of an arrest of the abnormal cell lines in these patients. The two apparently non-mosaic patients were, in fact, germ-cell mosaics. This suggests that the cytogenetic criteria used to define non-mosaic patients may be inadequate; thus, the risk of intracytoplasmic sperm injection in apparently non-mosaics may be lower than expected.

The evolution of mammalian sex chromosomes and the origin of sex determining genes

Abstract: Mammals have XX female: XY male chromosomal sex determination in which a small heterochromatic Y controls male development. Only a few active genes have been identified on the Y, including the testis determining factor SRY and candidate spermatogenesis genes. These genes, as well as several pseudogenes, have close relatives on the X, confirming that the Y was originally homologous to the X, but has been progressively degraded. We used comparative gene mapping of sex chromosomes from the three major groups of extant mammals (eutherians, marsupials and monotremes) to deduce how the X and Y evolved from a pair of autosomes, and how SRY assumed control of sex determination. We found that part of the X, and a corresponding region of the Y chromosome, is shared by all mammals and must be very ancient, but part of the X (and Y) was added quite recently. I propose that a small original X and Y were enlarged by cycles of autosomal addition to one partner, recombination onto the other and continuing attrition of the compound Y. This addition-attrition hypothesis predicts that the pseudoautosomal region of the human X is merely a relic of the last addition, and that the gene content of the pseudoautosomal region may well differ in different mammalian lineages. The only genes which remained active on the conserved or added regions of the Y were those, like SRY, that evolved functions in male sex determination and differentiation distinct from the general functions of their X-linked partners. Although the vertebrate gonadogenesis pathway is highly conserved, its control circuitry has probably changed radically and rapidly in evolution.